Research article
Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource
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* Corresponding author: Georgia Chenevix-Trench Georgia.Trench@qimr.edu.au
1 Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia
2 Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
3 School of Psychology, University of Sydney, NSW, Australia
4 Women's and Children's Health Service, Subiaco and Centre for Human Genetics, Edith Cowen University, Joondalup, Western Australia, Australia
5 Breast Cancer Network Australia, Camberwell, Victoria, Australia
6 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia
7 SA Clinical Genetics Service, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, Australia, and Department of Paediatrics, University of Adelaide, Australia
8 Queensland Clinical Genetics Service, Royal Children's Hospital, Brisbane, Herston, Australia
9 Genetic Services of Western Australia, King Edward's Memorial Hospital, School of Paediatrics and Child Health, University of Western Australia, Perth, Subiaco, Australia
10 Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia
11 Familial Cancer Centre, Royal Melbourne Hospital, Parkville, Victoria, Australia
12 Division of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
13 School of Surgery and Pathology, University of Western Australia, Perth, Western Australia, Australia
14 Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria, Australia
15 The Queensland Institute of Medical Research, Brisbane, Queensland, Australia
16 Hereditary Cancer Clinic, Prince of Wales Hospital, Sydney, Australia
Breast Cancer Research 2006, 8:R12 doi:10.1186/bcr1377
Published: 13 February 2006Abstract
Introduction
The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comprehensive resource of epidemiological and clinical data with biospecimens from individuals at high risk of breast and/or ovarian cancer, and from their close relatives.
Methods
Epidemiological, family history and lifestyle data, as well as biospecimens, are collected from multiple-case breast cancer families ascertained through family cancer clinics in Australia and New Zealand. We used the Tyrer-Cuzick algorithms to assess the prospective risk of breast cancer in women in the kConFab cohort who were unaffected with breast cancer at the time of enrolment in the study.
Results
Of kConFab's first 822 families, 518 families had multiple cases of female breast cancer alone, 239 had cases of female breast and ovarian cancer, 37 had cases of female and male breast cancer, and 14 had both ovarian cancer as well as male and female breast cancer. Data are currently held for 11,422 people and germline DNAs for 7,389. Among the 812 families with at least one germline sample collected, the mean number of germline DNA samples collected per family is nine. Of the 747 families that have undergone some form of mutation screening, 229 (31%) carry a pathogenic or splice-site mutation in BRCA1 or BRCA2. Germline DNAs and data are stored from 773 proven carriers of BRCA1 or BRCA1 mutations. kConFab's fresh tissue bank includes 253 specimens of breast or ovarian tissue – both normal and malignant – including 126 from carriers of BRCA1 or BRCA2 mutations.
Conclusion
These kConFab resources are available to researchers anywhere in the world, who may apply to kConFab for biospecimens and data for use in ethically approved, peer-reviewed projects. A high calculated risk from the Tyrer-Cuzick algorithms correlated closely with the subsequent occurrence of breast cancer in BRCA1 and BRCA2 mutation positive families, but this was less evident in families in which no pathogenic BRCA1 or BRCA2 mutation has been detected.